In the current dietary recommendations for the treatment and prevention of Type 2 diabetes and its related complications, there is flexibility in the proportion of energy derived from monounsaturated fat and carbohydrate as a replacement for saturated fat. Over the last few years, several population studies have shown that subjects eating a lot of refined grains and processed foods have a much larger increase in waist circumference than those following a diet higher in monounsaturated fat, protein and carbohydrates rich in fibre and whole grain. In the present issue of Clinical Science, Sinitskaya and co-workers have demonstrated that, in normal-weight rodents categorized into groups of high-fat and medium-carbohydrate [53%/30% of energy as fat/carbohydrate; 19.66 kJ/g (4.7 kcal/g)], high-fat and low-carbohydrate [67%/9% of energy as fat/carbohydrate; 21.76 kJ/g (5.2 kcal/g)] and high-fat and carbohydrate-free [75%/0% of energy as fat/carbohydrate; 24.69 kJ/g (5.9 kcal/g)] diets, the high-fat diets containing carbohydrates were both obesogenic and diabetogenic, whereas the very-high-fat and carbohydrate-free diet was not obesogenic but led to insulin resistance and higher risk of cardiovascular disease. This finding may indicate that high-fat diets could easily give rise to an unhealthy diet when combined with carbohydrates, highlighting the significance of macronutrient composition, rather than caloric content, in high-fat diets.